NO Donors and Inhibitors to Study Imbalance of Nitrogen Stress and Antioxidant Defense in COPD

Chronic Obstructive Pulmonary Disease Clinical Trial

Official title:

A Double Blind, Crossover Placebo-controlled Study to Evaluate the Effect of L-arginine and Aminoguanidine on Bronchial and Alveolar Nitric Oxide and Nitric Oxide Metabolites

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00180635
• Other study ID #: 02-104-170903
• Status: Completed
• Phase: N/A
• Start date: October 2003
• Est. completion date: July 2006

Study information

• Verified date: July 2019
• Source: Imperial College London
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The primary aim of this study is to investigate the effects of oral and inhaled administration of L-arginine and of inhaled aminoguanidine on bronchial and alveolar exhaled NO and NO metabolites in exhaled breath condensate, induced sputum, nasal lavage and mouth wash fluid in healthy non-smokers, current smokers and patients with COPD.

Description:

Nitric oxide (NO) is produced by resident and inflammatory cells in the respiratory tract by the enzyme NO synthase (NOS), which exists in three isoforms: neuronal NOS (nNOS), inducible NOS (iNOS), and endothelial NOS. NO production is increased in patients with COPD, and the production of NO under oxidative stress conditions generates reactive nitrogen species that may amplify the inflammatory response in COPD.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: July 2006
• Est. primary completion date: July 2006
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 21 Years to 70 Years

Eligibility

Inclusion Criteria:

• Healthy non-smokers

• Normal spirometry (FEV1 >90 % predicted; exhaled NO bigger than or equal to 10 ppb; flow 50 ml/s)

• At risk (current smokers)

• Normal spirometry, with or without chronic symptoms (cough, sputum production)

• FEV1 reversibility of <15% after inhaled beta2-agonists*

• Moderate COPD

• FEV1 greater than or equal to 30% and < 80%

• FEV1/FVC < 70% predicted

• FEV1 reversibility of <15% after inhaled beta2-agonists

• With or without chronic symptoms (cough, sputum production, dyspnea)

• Able to comprehend and grant a written informed consent

Exclusion Criteria:

• Concomitant use or pre-treatment within the last 4 weeks with oral steroids

• Respiratory infection within 4 weeks prior to entry into the trial

• Females who are pregnant or lactating

• History of current or past drug or alcohol abuse

Related Conditions & MeSH terms

• Chronic Obstructive Pulmonary Disease
• Lung Diseases
• Lung Diseases, Obstructive
• Pulmonary Disease, Chronic Obstructive

Intervention

Drug:
• Aminoguanidine
500mg
• Placebos
2ml

Locations

Country	Name	City	State
United Kingdom	Section of Airway Disease, Asthma Lab, Imperial College London, Royal Brompton Hospital	London

Sponsors (1)

Lead Sponsor	Collaborator
Imperial College London

Country where clinical trial is conducted

United Kingdom, 

References & Publications (1)

Brindicci C, Ito K, Torre O, Barnes PJ, Kharitonov SA. Effects of aminoguanidine, an inhibitor of inducible nitric oxide synthase, on nitric oxide production and its metabolites in healthy control subjects, healthy smokers, and COPD patients. Chest. 2009 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Bronchial exhale nitric oxide (JNO)	Bronchial exhale nitric oxide (JNO) as assessed by Chemo luminescence	24 hours